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precursor B-lymphoblastic leukemia/lymphoblastic lymphoma (B-cell ALL)

Neoplasm of lymphoblasts committed to B cell lineage. Precursor B-cell lymphoblastic leukemia and lymhoblastic lymphoma are considered parts of a spectrum of a single biologic entity. Etiology: - unknown - genetic factor play a role Epidemiology: - ~80 - 85% of acute lymphoblastic leukemias - ~10% of lymphoblastic lymphomas Pathology: - ~80% of acute lymphoblastic leukemia - <20% lymphoblastic lymphoma - extramedullary involvement is frequent in B-ALL, particularly to CNS, lymph nodes, spleen, liver and gonads. - B-lymphoblastic lymphoma most frequently involves skin, bone, soft tissue and lymph nodes. Microscopic pathology: - medium sized cells - round/convoluted nuclei, inconspicuous nucleoli - scant cytoplasm - chromatin moderately condensed to dispersed - coarse azurophilic granules in ~10% cases - mitoses less frequent in bone marrow than in T cell ALL Immunophenotype: - surface immunoglobulin - - CD10 +/- - CD13 -/+ - CD19 + - CD20 -/+ - CD22 +/- - CD24 +/- - CD33 -/+ - CD34 +/- - CD79a + - TdT + - HLA-DR + Genetics: - t(1;14)(q21;q32) BCL9 - t(1;19) (q23;p13.3) PBX1/TCF3 - t(4;11) (q21;q23) AF4/MLL - t(9;22) (q34;q11.2) BCR/Abl - t(12;21) (p13;q22) TEL/AML1 - t(17;19) (q22;p13.3) HLF/TCF3 - t(8;9) (p22;p24) JAK2/PCM1 - inv(19)(p13;q13) TFPT/TCF3 - hypodiploidy/hyperdipoidy Genetic alterations associated with favorable prognosis: - hyperdiploidy 51 - 65 chromosomes - t(12;21) (p13;q22) chromosomal translocation Genetic alterations associated with moderate prognosis: - hyperdiploidy ~ 50 - triploidy - tetraploidy Genetic alterations associated with unfavorable prognosis: - t(1;19) (q23;p13.3) PBX1/TCF3 - t(4;11) (q21;q23) AF4/MLL - t(9;22) (q34;q11.2) BCR/Abl - hypodiploidy Clinical manifestations: - highly aggressive, potentially curable - B-ALL: - bone marrow failure: thrombocytopenia/anemia/neutropenia - lymphadenopathy - hepatomegaly - splenomegaly - bone pain - arthralgias - B-lymphoblastic lymphoma - most frequently skin, bone and lymph nodes - skin involvement may manifest as multiple nodules - % lymphoblasts in marrow <25% Laboratory: - CD22 blasts in specimen - cytoplasmic CD22 blasts in specimen - CD22 blasts in blood - cytoplasmic CD22 blasts in blood - CD22 blasts in bone marrow - cytoplasmic CD22 blasts in bone marrow Management: - see acute lymphoblastic leukemia - inotuzumab ozogamicin + dexamethasone induction therapy can result in complete remission in older adults with Philadelphia chromosome-negative precursor B-cell ALL - induction therapy includes 2 or 3 cycles of inotuzumab ozogamicin + dexamethasone, followed by age-adapted consolidation (5 cycles), late intensification (1 cycle), & maintenance chemotherapy (up to 2 years) [5] - intrathecal chemotherapy prophylaxis administered all treatment phases - adult who have failed chemotherapy - autologous transformed T-cells show promise [3] - harvested T-cell transformed with a virus, to express CD19 on their surface are reintroduced to the patient - the T-cells subsequetnly attack and kill the malignant B-cells [3] - induced remission may allow patients to become eligible for bone marrow transplantation [3] - same strategy applied to children with ALL [4] - emergence of leukemic blasts not expressing CD19 associated with relapse [4]

Interactions

disease interactions

General

acute lymphoblastic leukemia (ALL) lymphoblastic lymphoma precursor B-cell lymphoid neoplasm

References

  1. Chan JK, Banks PM, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Harris NL, Isaacson PG, et al. A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group. A summary version. Am J Clin Pathol. 1995 May;103(5):543-60. PMID: 7741099
  2. WHO Classification Tumours of Haematopoietic and Lymphoid Tissues. IARC Press 2001
  3. Brentjens RJ et al CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia. Sci Transl Med 20 March 2013 5:177ra38 PMID: 23515080 http://stm.sciencemag.org/search?author1=Renier+J.+Brentjens&sortspec=date&submit=Submit
  4. Grupp SA et al Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia. N Engl J Med. March 25, 2013 PMID: 23527958 http://www.nejm.org/doi/full/10.1056/NEJMoa1215134
  5. Stelljes M et al. Inotuzumab ozogamicin as induction therapy for patients older than 55 years with Philadelphia chromosome-negative B-precursor ALL. J Clin Oncol 2024 Jan 20; 42:273 PMID: 37883727 https://ascopubs.org/doi/10.1200/JCO.23.00546 - Logan A. Innovating simpler and less toxic frontline management for adults with ALL. J Clin Oncol 2024 Jan 20; 42:250. PMID: 37883737 https://ascopubs.org/doi/10.1200/JCO.23.01726